Priprava, karakterizacija i interakcije 3-aminopropil dekladinozil derivata azitromicina s ribosomom iz bakterije Escherichia coli

master's thesis

• Title (english): Synthesis, characterization and interactions of 3-aminopropyl descladinosyl derivate of azithromycin with Escherichia coli ribosome
• Author: Jana Gašperov
• Mentor: Predrag Novak (mentor)
• Committee member: Predrag Novak (predsjednik povjerenstva)
• Committee member: Đani Škalamera (član povjerenstva)
• Committee member: Ivica Đilović (član povjerenstva)
• Committee member: Tomislav Jednačak (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Chemistry); Zagreb
• Defense date and country: 2020-12-08, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Chemistry

Abstract

Makrolidni antibiotici, poput azitromicina, koriste se u liječenju infekcija uzrokovanih Gram-pozitivnim i Gram-negativnim bakterijama. Djeluju kao inhibitori sinteze bakterijskih proteina tako što se vežu na 50S podjedinicu bakterijskog ribosoma u blizini centra peptidil-transferaze. Učestalo korištenje makrolidnih antibiotika dovelo je do pojave i razvoja bakterijske rezistencije. Iz tog razloga javlja se potreba za otkrićem i razvojem novih antibiotika. Za razumijevanje cjelokupnog biološkog profila novog potencijalnog lijeka važno je odrediti konformaciju molekule u slobodnom i vezanom stanju te istražiti interakcije s biološkim metama. U ovom radu uspješno je pripravljen 3-aminopropil dekladinozil derivat azitromicina (S6), prekursor u sintezi makrozona, novih bioaktivnih konjugata azitromicina i tiosemikarbazona. Pripravljeni spoj okarakteriziran je spektroskopijom NMR i spektrometrijom masa. Upotrebom tehnike ROESY određena je konformacija prekursora u slobodnom stanju, a pomoću tehnika tr-NOESY i STD istražene su interakcije prekursora s ribosomom izoliranim iz bakterije Escherichia coli te je određena konformacija u vezanom stanju.

Abstract (english)

Macrolide antibiotics, such as azithromycin, are used to treat infections caused by Gram-positive and Gram-negative bacteria. They act as inhibitors of bacterial protein synthesis by binding to the 50S subunit of the bacterial ribosome at or near the peptidyl transferase center. Frequent use of macrolide antibiotics has led to the emergence of bacterial resistance. For this reason, there is a need to discover and develop new antibiotics. To understand the overall biological profile of a new potential drug, it is important to determine the conformation of molecules in the free and bound state and to investigate interactions with biological targets. In this work, 3-aminopropyl decladinosyl derivative of azithromycin (S6), a precursor in the synthesis of macrozones, a new bioactive conjugate of azithromycin and thiosemicarbazone, was successfully prepared. The compound S6 was characterized by NMR spectroscopy and mass spectrometry. ROESY technique was applied to estimate free conformation in solution. The interactions of S6 with the ribosome isolated from Escherichia coli were investigated by using tr-NOESY and STD techniques. The analysis of the recorded spectra enabled determination of conformation in bound state.

• Keywords: azitromicin; interakcije; makrolidi; rezistencija; spektroskopija NMR
• Keywords (english): azithromycin; interactions; macrolides; resistance; spectroscopy NMR
• Language: croatian
• URN:NBN: urn:nbn:hr:217:785839
• Study programme: Title: Graduate university studies in chemistry; specializations in: Research programme; Course: Research programme; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra kemije (magistar/magistra kemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2021-02-15 11:55:05